Imaging the Effect of HSP90 Inhibitor AUY922 on VEGF by Means of 89Zr-bevacizumab PET
This feasibility study is designed as a side study to the multicenter, international phase
I-II trial with HSP90 inhibitor AUY922 (protocol CAUY922A2101), as part of the biomarker
assessment. In protocol CAUY922A2101, section 4, the design of this phase I-II trial is
described (p37, 38). Briefly, a dose-escalation study is performed according to phase I
design in adult patients with advanced solid malignancies. This part is followed by a
dose-expansion study according to a phase II design. In the latter part, breast cancer
patients are enrolled that are either refractory to hormone- or trastuzumab treatment (both
treatment arms, n=40 patients), on the maximal tolerated dose of AUY922 based on the phase I
part of the study. Patients with ER positive, hormone therapy refractory breast cancer, will
receive a 89Zr-bevacizumab PET scan as part of the present side study protocol, which will
be performed in collaboration with the Royal Marsden Hospital (United Kingdom).
To this end, a 89Zr-bevacizumab PET scan will be performed before (baseline) and during
treatment with HSP90 inhibitor AUY922, as described below.
A minimum of six patients will be entered to evaluate whether the effect of HSP90 inhibition
by AUY922 can be detected with a 89Zr-bevacizumab PET scan
Observational Model: Cohort, Time Perspective: Prospective
To evaluate the effect of HSP90 inhibition by AUY922 on VEGF by means of 89Zr-bevacizumab PET.
Primary endpoint: measurement of decreased VEGF compared to baseline. A decline is defined as a decrease of at least 30% in mean Standardized Uptake Value (SUV) in a maximum of three lesions.
C.P. Schröder, PhD
University Medical Centre Groningen
Netherlands: Medical Ethics Review Committee (METC)